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MicroRNA expression profiles associated with development of drug resistance in Ehrlich ascites tumor cells

Husted, Susanne; Søkilde, Rolf LU ; Rask, Lene; Cirera, Susanna; Busk, Peter Kamp; Eriksen, Jens and Litman, Thomas (2011) In Molecular Pharmaceutics 8(6). p.62-2055
Abstract

Multidrug resistance (MDR) poses a major obstacle to successful chemotherapeutic treatment of cancer, and often involves multiple genes, which may be regulated post-transcriptionally by microRNAs (miRNAs). The purpose of the present study was therefore to identify any resistance-associated changes in miRNA expression in a sensitive and five increasingly drug-resistant Ehrlich ascites tumor (EAT) cell lines, representing different steps in the development of resistance. We used an LNA-enhanced microarray platform to study the global miRNA expression profiles in the six murine EAT cell lines, and identified growth-, hypoxia-, and resistance-specific miRNA patterns. Among the differentially expressed miRNAs, we found the two clusters... (More)

Multidrug resistance (MDR) poses a major obstacle to successful chemotherapeutic treatment of cancer, and often involves multiple genes, which may be regulated post-transcriptionally by microRNAs (miRNAs). The purpose of the present study was therefore to identify any resistance-associated changes in miRNA expression in a sensitive and five increasingly drug-resistant Ehrlich ascites tumor (EAT) cell lines, representing different steps in the development of resistance. We used an LNA-enhanced microarray platform to study the global miRNA expression profiles in the six murine EAT cell lines, and identified growth-, hypoxia-, and resistance-specific miRNA patterns. Among the differentially expressed miRNAs, we found the two clusters miR-183∼miR-96∼miR-182 and miR-200b∼miR-200a∼miR-429 as well as miR-141 to be consistently upregulated in the MDR cell lines, while miR-125b-5p and the two clusters miR-30d∼miR-30b and miR-23b∼miR-27b∼miR-24-1 were downregulated in most of the resistant EAT cells. Several of the target genes for these miRNAs-including Zeb1/Zeb2 and members of the Fox gene family-could contribute to the drug-resistant phenotype, although we did not find that the degree of resistance was directly correlated to any specific changes in miRNA expression. Probably, the observed miRNA expression patterns reflect the underlying genomic instability of the tumor cells, and further studies are needed to explore how the highly complex regulatory miRNA networks contribute to the development of MDR.

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author
publishing date
type
Contribution to journal
publication status
published
keywords
Animals, Antineoplastic Agents, Carcinoma, Ehrlich Tumor, Cell Line, Tumor, Cisplatin, Doxorubicin, Drug Resistance, Neoplasm, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Mice, MicroRNAs, Reverse Transcriptase Polymerase Chain Reaction, Journal Article, Research Support, Non-U.S. Gov't
in
Molecular Pharmaceutics
volume
8
issue
6
pages
8 pages
publisher
The American Chemical Society
external identifiers
  • scopus:82955240683
ISSN
1543-8392
DOI
10.1021/mp200255d
language
English
LU publication?
no
id
d4530d3c-bba9-45fe-8f0f-7074a753a174
date added to LUP
2017-09-01 14:30:03
date last changed
2017-09-11 12:36:06
@article{d4530d3c-bba9-45fe-8f0f-7074a753a174,
  abstract     = {<p>Multidrug resistance (MDR) poses a major obstacle to successful chemotherapeutic treatment of cancer, and often involves multiple genes, which may be regulated post-transcriptionally by microRNAs (miRNAs). The purpose of the present study was therefore to identify any resistance-associated changes in miRNA expression in a sensitive and five increasingly drug-resistant Ehrlich ascites tumor (EAT) cell lines, representing different steps in the development of resistance. We used an LNA-enhanced microarray platform to study the global miRNA expression profiles in the six murine EAT cell lines, and identified growth-, hypoxia-, and resistance-specific miRNA patterns. Among the differentially expressed miRNAs, we found the two clusters miR-183∼miR-96∼miR-182 and miR-200b∼miR-200a∼miR-429 as well as miR-141 to be consistently upregulated in the MDR cell lines, while miR-125b-5p and the two clusters miR-30d∼miR-30b and miR-23b∼miR-27b∼miR-24-1 were downregulated in most of the resistant EAT cells. Several of the target genes for these miRNAs-including Zeb1/Zeb2 and members of the Fox gene family-could contribute to the drug-resistant phenotype, although we did not find that the degree of resistance was directly correlated to any specific changes in miRNA expression. Probably, the observed miRNA expression patterns reflect the underlying genomic instability of the tumor cells, and further studies are needed to explore how the highly complex regulatory miRNA networks contribute to the development of MDR.</p>},
  author       = {Husted, Susanne and Søkilde, Rolf and Rask, Lene and Cirera, Susanna and Busk, Peter Kamp and Eriksen, Jens and Litman, Thomas},
  issn         = {1543-8392},
  keyword      = {Animals,Antineoplastic Agents,Carcinoma, Ehrlich Tumor,Cell Line, Tumor,Cisplatin,Doxorubicin,Drug Resistance, Neoplasm,Gene Expression Profiling,Gene Expression Regulation, Neoplastic,Humans,Mice,MicroRNAs,Reverse Transcriptase Polymerase Chain Reaction,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  month        = {12},
  number       = {6},
  pages        = {62--2055},
  publisher    = {The American Chemical Society},
  series       = {Molecular Pharmaceutics},
  title        = {MicroRNA expression profiles associated with development of drug resistance in Ehrlich ascites tumor cells},
  url          = {http://dx.doi.org/10.1021/mp200255d},
  volume       = {8},
  year         = {2011},
}